Modeling Prognostic Factors in Resectable Pancreatic Adenocarcinomas

BACKGROUND: The accurate prognosis for patients with resectable pancreatic adenocarcinomas requires the incorporation of more factors than those included in AJCC TNM system. METHODS: We identified 218 patients diagnosed with stage I and II pancreatic adenocarcinoma at NewYork-Presbyterian Hospital/Columbia University Medical Center (1999 to 2009). Tumor and clinical characteristics were retrieved and associations with survival were assessed by univariate Cox analysis. A multivariable model was constructed and a prognostic score was calculated; the prognostic strength of our model was assessed with the concordance index. RESULTS: Our cohort had a median age of 67 years and consisted of 49% men; the median follow-up time was 14.3 months and the 5-year survival 3.6%. Age, tumor differentiation and size, alkaline phosphatase, albumin and CA 19-9 were the independent factors of the final multivariable model; patients were thus classified into low (n = 14, median survival = 53.7 months), intermediate (n = 124, median survival = 19.7 months) and high risk groups (n = 80, median survival = 12.3 months). The prognostic classification of our model remained significant after adjusting for adjuvant chemotherapy and the concordance index was 0.73 compared to 0.59 of the TNM system. CONCLUSION: Our prognostic model was accurate in stratifying patients by risk and could be incorporated into clinical decisions

Primary HT and risk for breast cancer: a systematic review and meta-analysis

Objective: The association between hypothyroidism and breast cancer has been described from very early on. Breast and thyroid tissue are interconnected on a molecular level mainly through activation of thyroid hormone receptors expressed on cells of the mammary gland as well as on the plasma membrane of breast cancer cells. Despite the experimental evidence the true value of hypothyroidism as a risk factor for breast cancer remains controversial. Methods: We searched the PubMed database through February 2011 to identify studies that evaluated the association between hypothyroidism and risk for breast cancer as well as the effect of thyroid hormone replacement therapy on breast cancer incidence. Results: A meta-analysis performed in 12 studies showed that hypothyroidism was not associated with risk for breast cancer (pooled risk ratio (RR) = 1.06, 95% confidence intervals (CIs) 0.82-1.35, P = 0.672). The effect of treatment was assessed in seven studies and no evidence for an association between thyroid hormone replacement and breast cancer was observed with an overall RR of 0.99 (95% CI 0.73-1.35, P = 0.965). Conclusions: Our meta-analysis showed that hypothyroidism is not associated with increased risk for breast cancer and thyroid hormone replacement therapy does not reduce breast cancer prevalence; however, the heterogeneity of the studies analyzed precludes firm conclusions

Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro

We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC). Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA). Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC 50) when exposed to the majority of single-agent chemotherapies. High HER-2/neu expressors were more sensitive to platinum compounds, manifesting a 5.22-fold decrease in carboplatin-IC 50 ( P = .005) and a 5.37-fold decrease in cisplatin-IC 50 ( P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC 50 when used in combination than as individual agents. USPC overexpressing HER-2/neu display greater in vitro sensitivity to platinum compounds when compared to low HER-2/neu expressors. Higher proliferative capability rather than increased drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in USPC

High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

Abstract Background Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Methods Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA®, a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Results Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Conclusions Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.</p